1. Field of the Invention
The present invention concerns 2'-0-(4-benzoyl)benzoyl nucleoside cyclic monophosphate and the use of the same as to reduce intraocular pressure
2.Background of the Invention
The first report of benzoyl benzoyl derivatization was of the peptide hormone gastrin. This compound is unrelated to cyclic nucleotides and was employed as a photoaffinity probe for the gastrin receptor (R. E. Galardy, L. C. Craig, J. D. Jamieson and M. P. Printz, J. Biol. Chem., 249, 3510, (1974)). Benzoyl benzoyl derivatives of adenosine 5'triphosphate (ATP) (N. Williams and P. S. Coleman, J. Biol. Chem., 257, 2834-2841, (1982)), cytidine triphosphate (CTP) (C. Abeijon, J. M. Capasso, D. Tal, W. F. Vann and C. B. Hirschberg, J. Biol. Chem., 261, 11374-11377, (1986)) and uridine 5'triphosphate (UTP) (C. Abeijon et al, supra) were subsequntly reported. In each of these nucleotide triphosphates, the benzoyl benzoyl moiety was added at the 3'position. Fluorobenzoyl adenosine 5'triphosphate has been synthesized, but the fluorobenzoyl moiety was added to the N.sup.6 position on the base.
Derivatives of 3',5'cyclic guanosine monophosphate (cGMP) and 3',5'cyclic adenosine monophosphate (cAMP) which are useful as photoaffinity agents have been synthesized. Such derivatives differ from the inventive compounds herein in either the nature or location of the substituent moieties added. A thorough treatment of photoaffinity labelling compounds can be found in Methods of Enzymology, Vol. XLVI, (1977), Academic Press, N.Y., eds. W. B. Jakoby and Meir Wilchek. Some examples of these kinds of compounds are 8-azido derivatives of both cAMP and cGMP (B. E. Haley, Biochemistry, 14, 3852, (1975) and B. E. Haley, Methods in Enzymology, XLVI, 339-346, (1977)) and methylanthraniloyl addition to the 2'position of cGMP and cAMP (T. Hiratsuka, J. Biol. Chem., 257, 11354-13358, (1982)). Two fluorescent analogs of cAMP, 1,N-etheno-cAMP (J. A. Secrist, III, J. R. Barrio, N. J. Leonard, C. Villar-Palasi and A. G. Gilman, Science, 177, 279-280, (1972)) and 1,N-etheno-aza-cAMP (K. C. Tsou, K. F. Yip and L. W. Lo, Anal. Biochem., 60, 163-169, (1974)) have been reported, however, both analogs have altered adenine ring structures.
None of the above described heretofore reported compounds have been employed as therapeutic agents for the treatment of glaucoma or any other medical condition.